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Z H Lin, H Liu, L Zhu, X Yang, Y P Zhang, J Qian, H Y Liu
Objective: To explore the effects and possible mechanism of rapamycin (RAPA) on apoptosis of CD4+ CD25+ Tregs from the mouse severe aplastic anemia (SAA) model. Methods: The BALB/c female SAA model mice were induced by interferon-gamma in combination with busulphan. The SAA model mice were intraperitoneal injection with RAPA at daily dose of 0.5 mg/kg for 5 days (the RAPA-treated group, n =15) in the SAA group ( n =15) and the un-treated group ( n =15) were control. Bone marrow hematopoiesis changes were observed by the patho-morphological examination of femurs...
March 14, 2018: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
Liansheng Liu, Jinqiu Lu, Xiaoling Li, Ailing Wu, Qingzhe Wu, Mujun Zhao, Nan Tang, Hai Song
Intracellular transport of membranous organelles and protein complexes to various destinations is fundamental to signaling transduction and cellular function. The cytoplasmic dynein motor and its regulatory proteins LIS1 and NDE1 are required for transporting a variety of cellular cargos along the microtubule network. In this study, we show that deletion of Lis1 in developing lung endoderm and limb mesenchymal cells causes agenesis of the lungs and limbs. In both mutants, there is increased cell death and decreased fibroblast growth factor (FGF) signaling activity...
March 20, 2018: Cell Reports
Julius A Edson, Dominique Ingato, Shirley Wu, Bianca Lee, Young Jik Kwon
Despite its promises for biomedical applications, the lack of solubility in a physiological solution, the limited molecular interactions with nucleic acids due to the rigid backbone, and the inefficient intracellular release limits the use of chitosan, a natural cationic polysaccharide, for gene delivery. In this study, a flexible, aqueous-soluble aminoethoxy branch was conjugated to the primary hydroxyl group of chitosan via an acid-cleavable ketal linkage, resulting in acid-transforming chitosan (ATC) with greatly increased aqueous solubility, improved siRNA complexation, and degradability in response to an acidic pH...
March 21, 2018: Biomacromolecules
Mihaela Skrt, Polona Jamnik, Nataša Poklar Ulrih
The hyperthermophilic archaeon Aeropyrum pernix has adapted to optimal growth under high temperatures in saline environments and under oxidizing conditions. In the present study, we focused on the antioxidative activity of proteins from A. pernix K1. Following high temperature methanol and water extractions of the protein from the biomass of A. pernix K1, the total sulphydryl groups and radical scavenging activities were investigated. The total protein in the methanolic extract was 36% lower and showed 10% fewer sulphydryl groups than that from the water extract...
March 2018: Acta Chimica Slovenica
J L de Deus, A L A Dagostin, W A Varanda
Testosterone synthesis within Leydig cells is a calcium-dependent process. Intracellular calcium levels are regulated by different processes including ATP-activated P2X purinergic receptors, T-type Ca2+ channels modulated by the luteinizing hormone, and intracellular calcium storages recruited by a calcium-induced calcium release mechanism. On the other hand, nitric oxide (NO) is reported to have an inhibitory role in testosterone production. Based on these observations, we investigated the interaction between the purinergic and nitrergic systems in Leydig cells of adult mice...
March 15, 2018: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
Ayako Casanova-Nakayama, Elena Wernicke von Siebenthal, Christian Kropf, Elisabeth Oldenberg, Helmut Segner
Genomic actions of estrogens in vertebrates are exerted via two intracellular estrogen receptor (ER) subtypes, ERα and ERβ, which show cell- and tissue-specific expression profiles. Mammalian immune cells express ERs and are responsive to estrogens. More recently, evidence became available that ERs are also present in the immune organs and cells of teleost fish, suggesting that the immunomodulatory function of estrogens has been conserved throughout vertebrate evolution. For a better understanding of the sensitivity and the responsiveness of the fish immune system to estrogens, more insight is needed on the abundance of ERs in the fish immune system, the cellular ratios of the ER subtypes, and their autoregulation by estrogens...
March 21, 2018: International Journal of Molecular Sciences
Amelia R I Lindsey, Tamanash Bhattacharya, Irene L G Newton, Richard W Hardy
At the forefront of vector control efforts are strategies that leverage host-microbe associations to reduce vectorial capacity. The most promising of these efforts employs Wolbachia , a maternally transmitted endosymbiotic bacterium naturally found in 40% of insects. Wolbachia can spread through a population of insects while simultaneously inhibiting the replication of viruses within its host. Despite successes in using Wolbachia -transfected mosquitoes to limit dengue, Zika, and chikungunya transmission, the mechanisms behind pathogen-blocking have not been fully characterized...
March 21, 2018: Viruses
Leonardo C de Oliveira, Bruno S A F Brasil, Bethany Unger, Giliane S Trindade, Jonatas S Abrahão, Erna G Kroon, Paula Traktman, Cláudio A Bonjardim
Evolution has equipped poxvirus genomes with the coding capacity for several virus-host interaction products which interfere with host cell gene expression and protein function, creating an adequate intracellular environment for a productive infection. We show here that Vaccinia virus (VACV) induces the expression of the cellular transcription factor EGR-1 (early growth response-1) in Mouse Embryonic Fibroblasts (MEFs) through the MEK (mitogen-activated protein kinase (MAPK)/ERK)/ERK (extracellular signal-regulated kinases) pathway, from 3 to 12 h post infection (h...
March 21, 2018: Viruses
Shufang He, Weiwei Fan, Na Wu, Jingjing Zhu, Yunqiu Miao, Xiaran Miao, Feifei Li, Xinxin Zhang, Yong Gan
RNA interference (RNAi) technology has shown great promise for the treatment of cancer and other genetic disorders. Despite the efforts to increase the target tissue distribution, the safe and effective delivery of siRNA to the diseased cells with sufficient cytosolic transport is another critical factor for successful RNAi clinical application. Here, the constructed lipid-based liquid crystalline nanoparticles, called nano-Transformers, can transform the structure in the intracellular acidic environment, and perform high-efficient siRNA delivery for cancer treatment...
March 21, 2018: Nano Letters
Eduardo Guisasola, Laura Asín, Lillianne Beola, Jesús M De La Fuente, Alejandro Baeza, María Vallet Regí
This work presents an innovation in the tumor treatment in vivo mediated by magnetic mesoporous silica nanoparticles (MMSNs). This device was built with iron oxide magnetic nanoparticles embedded in a mesoporous silica matrix and coated with an engineered thermoresponsive polymer. The magnetic nanoparticles act as internal heating sources under an alternating magnetic field (AMF) that increase the temperature of the surroundings, provoking the polymer transition and consequently the release of a drug trapped inside the silica pores...
March 21, 2018: ACS Applied Materials & Interfaces
Hunter G Moss, Truman R Brown, Donald B Wiest, Dorothea D Jenkins
Persistent oxidative stress depletes reduced glutathione (GSH), an intracellular antioxidant and an important determinant of CNS injury after hypoxia ischemia. We used standard, short echo time Stimulated Echo Acquisition Mode (STEAM) to detect GSH by magnetic resonance spectroscopy (MRS) in 24 term neonates with hypoxic-ischemic encephalopathy (HIE), on day of life 5-6, after rewarming from therapeutic hypothermia. MRS demonstrated reliable, consistent GSH of 1·64 ± 0·20 mM in the basal ganglia immediately before intravenous infusion of N-acetylcysteine...
January 1, 2018: Journal of Cerebral Blood Flow and Metabolism
Jindan Li, Zijuan Hai, Huiqiong Xiao, Xiaoyi Yi, Gaolin Liang
Nanoprobes are advantageous over small molecular probes in sensitivity but most luminescence molecules used to construct nanoprobes often suffer from an aggregation-caused quenching effect. Herein, we rationally designed a small molecular probe Cys(StBu)-Lys(Ru(bpy)32+)-CBT (1) which "smartly" self-assembled into nanoparticles 1-NPs inside cells with non-quenched, persistent phosphorescence. Employing this property, we successfully applied 1 for long-term sensing of biothiol activity in living HepG2 cells and tumors...
March 21, 2018: Chemical Communications: Chem Comm
Linlin Yang, Jun Zhao, Xinling Yu, Ruilong Zhang, Guangmei Han, Renyong Liu, Zhengjie Liu, Tingting Zhao, Ming-Yong Han, Zhongping Zhang
Hydrogen sulfide (H2S) is a key signaling molecule in the cytoprotection, vascular mediation and neurotransmission of living organisms. In-depth understanding of its production, trafficking, and transformation in cells is very important in the way H2S mediates cellular signal transductions and organism functions; it also motivates the development of H2S probes and imaging technologies. A fundamental challenge, however, is how to engineer probes with sensitivity and cellular penetrability that allow detection of spontaneous production of H2S in the entire cell space and live animals...
March 21, 2018: Analyst
Raghav R Poudyal, Fatma Pir Cakmak, Christine D Keating, Philip C Bevilacqua
This Perspective focuses on RNA in biological and nonbiological compartments resulting from liquid-liquid phase separation (LLPS), with an emphasis on origins of life. In extant cells, intracellular liquid condensates, many of which are rich in RNAs and intrinsically disordered proteins, provide spatial regulation of biomolecular interactions that can result in altered gene expression. Given the diversity of biogenic and abiogenic molecules that undergo LLPS, such membraneless compartments may have also played key roles in prebiotic chemistries relevant to the origins of life...
March 21, 2018: Biochemistry
Delphine Masschaele, Joris Wauman, Giel Vandemoortele, Delphine De Sutter, Leentje De Ceuninck, Sven Eyckerman, Jan Tavernier
Ring finger protein 41 (RNF41) is an E3 ubiquitin ligase involved in the ubiquitination and degradation of many proteins including ErbB3 receptors, BRUCE and parkin. Next to this, RNF41 regulates the intracellular trafficking of certain JAK2-associated cytokine receptors by ubiquitinating and suppressing USP8 which in turn destabilizes the ESCRT-0 complex. To further elucidate the function of RNF41 we used different orthogonal approaches to reveal the RNF41 protein complex: Affinity Purification-Mass Spectrometry, BioID and Virotrap...
March 21, 2018: Journal of Proteome Research
Ina Bähr, Janine Jahn, Alexander Zipprich, Inge Pahlow, Julia Spielmann, Heike Kielstein
Obesity is associated with alterations in functionality of immune cells, like macrophages and natural killer (NK) cells, leading to an increased risk for severe infections and several cancer types. This study aimed to examine immune cell populations and functional NK cell parameters focusing on NK cell subset phenotypes in normal-weight and obese humans. Therefore, peripheral blood mononuclear cells (PBMCs) were isolated from normal-weight and obese individuals and analyzed by flow cytometry. Results show no significant changes in the frequency of monocytes, B lymphocytes, or NKT cells but a significantly increased frequency of T lymphocytes in obesity...
March 20, 2018: Immunologic Research
Daisuke Ono, Ken-Ichi Honma, Yuchio Yanagawa, Akihiro Yamanaka, Sato Honma
In mammals, circadian rhythms, such as sleep/wake cycles, are regulated by the central circadian clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus. The SCN consists of thousands of individual neurons, which exhibit circadian rhythms. They synchronize with each other and produce robust and stable oscillations. Although several neurotransmitters are expressed in the SCN, almost all SCN neurons are γ-amino butyric acid (GABA)-ergic. Several studies have attempted to understand the roles of GABA in the SCN; however, precise mechanisms of the action of GABA in the SCN are still unclear...
March 20, 2018: Journal of Physiological Sciences: JPS
Eva Skiöldebrand, Anna Thorfve, Ulrika Björklund, Pegah Johansson, Ruth Wickelgren, Anders Lindahl, Elisabeth Hansson
Chondrocytes are effectively involved in the pathophysiological processes of inflammation in joints. They form cellular processes in the superficial layer of the articular cartilage and form gap junction coupled syncytium to facilitate cell-to-cell communication. However, very little is known about their physiological cellular identity and communication. The aim with the present work is to evaluate the physiological behavior after stimulation with the inflammatory inducers interleukin-1β and lipopolysaccharide...
January 2018: Heliyon
Yoichi Ohshima, Katsutoshi Taguchi, Ikuko Mizuta, Masaki Tanaka, Takami Tomiyama, Fuyuki Kametani, Chihiro Yabe-Nishimura, Toshiki Mizuno, Takahiko Tokuda
Soluble oligomers of amyloid-β (Aβ) peptides (AβOs) contribute to neurotoxicity in Alzheimer's disease (AD). However, it currently remains unknown whether an increase in AβOs is the common phenotype in cellular and animal models. Furthermore, it has not yet been established whether experimental studies conducted using models overexpressing mutant genes of the amyloid precursor protein (APP) are suitable for investigating the underlying molecular mechanism of AD. We herein employed the Flp-In™ T-REx™-293 (T-REx 293) cellular system transfected with a single copy of wild-type, Swedish-, Dutch-, or London-type APP , and quantified the levels of Aβ monomers (Aβ1-40 and Aβ1-42) and AβOs using an enzyme-linked immunosorbent assay (ELISA)...
January 2018: Heliyon
Ioannis Panagopoulos, Ludmila Gorunova, Hege Kilen Andersen, Astrid Bergrem, Anders Dahm, Kristin Andersen, Francesca Micci, Sverre Heim
Background: Acquired primary chromosomal changes in cancer are sometimes found as sole karyotypic abnormalities. They are specifically associated with particular types of neoplasia, essential in establishing the neoplasm, and they often lead to the generation of chimeric genes of pathogenetic, diagnostic, and prognostic importance. Thus, the report of new primary cancer-specific chromosomal aberrations is not only of scientific but also potentially of clinical interest, as is the detection of their gene-level consequences...
2018: Experimental Hematology & Oncology
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